Soluble antigen arrays disarm antigen-specific B cells to promote lasting immune tolerance in experimental autoimmune encephalomyelitis

Journal of Autoimmunity
Brittany HartwellCory Berkland

Abstract

Autoreactive lymphocytes that escape central immune tolerance may be silenced via an endogenous peripheral tolerance mechanism known as anergy. Antigen-specific therapies capable of inducing anergy may restore patients with autoimmune diseases to a healthy phenotype while avoiding deleterious side effects associated with global immunosuppression. Inducing anergy in B cells may be a particularly potent intervention, as B cells can contribute to autoimmune diseases through multiple mechanisms and offer the potential for direct antigen-specific targeting through the B cell receptor (BCR). Our previous results suggested autoreactive B cells may be silenced by multivalent 'soluble antigen arrays' (SAgAs), which are polymer conjugates displaying multiple copies of autoantigen with or without a secondary peptide that blocks intracellular cell-adhesion molecule-1 (ICAM-1). Here, key therapeutic molecular properties of SAgAs were identified and linked to the immunological mechanism through comprehensive cellular and in vivo analyses. We determined non-hydrolyzable 'cSAgAs' displaying multivalent 'click'-conjugated antigen more potently suppressed experimental autoimmune encephalomyelitis (EAE) compared to hydrolyzable SAgAs capable of r...Continue Reading

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Citations

Jan 4, 2019·Advanced Healthcare Materials·Joshua M Gammon, Christopher M Jewell
Mar 19, 2019·Annual Review of Cell and Developmental Biology·Andrew Getahun, John C Cambier
Jun 4, 2020·Brain Sciences·Olga Kammona, Costas Kiparissides
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Nov 13, 2020·Biomaterials Science·Amy E EmersonJessica D Weaver
Apr 24, 2020·Advanced Drug Delivery Reviews·J Daniel GriffinCory J Berkland
May 22, 2021·Diabetes·Roberto Mallone, Sylvaine You
Jan 27, 2019·Molecular Pharmaceutics·Martin A LeonCory Berkland
Sep 10, 2020·Molecular Pharmaceutics·Matthew A ChristopherCory J Berkland
Jul 2, 2019·ACS Chemical Biology·Martin A LeonCory Berkland

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